STRESS

What is stress?

Physical stressors Illness Surgery Cold Heat Hunger Competitive athletics Fighting Fleeing

Fight or run away? image from: naturescrusaders.wordpress.comnaturescrusaders.wordpress.com

Psychological stressors Any new experience (potentially) Anticipation of something previously experienced as unpleasant Situations in which rules are changed or previous behavior no longer effective Fighting or observing others fighting Crowding Acute situations: airplane flight, exam, new situations, competitive athletics, workdays vs weekends Chronic life situations (divorce, death in the family, illness in the family) Note : Context matters

Context matters Dominance versus submissionPrevious experience Images from: Competitive sports

Fig involved in processing memories related to stress amygdala

Physiological responses to stress Increased rate and contractility of the heart Alterations in blood flow distribution Increased gluconeogenesis (synthesis of glucose) Mobilization of amino acids (used to synthesize glucose) Increased muscle contractility and decreased fatiguability Increased learning and memory

Stress Hypothalamus Sympathetic nervous system CRH Epinephrine/norepinephrine ACTH cortisol

image at: Location of adrenal glands

Effects of epinephrine Increased heart rate and contractility Effects on arteriolar smooth muscle Widens pupil and flattens lens (far vision) Decreases GI motility Promotes glucose synthesis Increases central nervous system activity Decreases fatigue of skeletal muscle

Diurnal variations in plasma cortisol

growth of adrenal cortex

Effects of cortisol Increased plasma glucose Increased contractility of skeletal and cardiac muscle Inhibits bone growth Inhibits protein synthesis, accelerates protein degradation - inhibits collagen formation, easy bruising Required for maintenance of blood pressure CNS effects on learning and other responses Increases gastric secretions Modulates inflammatory and immune responses

Some conditions in which corticosteroids are useful Allergic disorders (asthma, atopic dermatitis) Gastrointestinal disorders (Crohn’s disease, ulcerative colitis) Arthritis Skin irritations

Typical course of prednisone treatment (oral corticosteroid) image at: Why is it necessary to “taper off” Day 6 Day 5 Day 4 Day 3 Day 2 Day 1

growth of adrenal cortex

From: McEwen, B.S. Ann Rev Med 62: , 2011 Allostatic load: toll on the body due to physiological responses to stress

Differences between physical and psychological stressors

Effects of chronic stress GI system: worsens ulcers Immune system: immunosuppression (increased autoimmune diseases, increased infections) Endocrine system: type II diabetes Growth: retards growth in children, induces weight and bone loss in adults Cardiovascular system: Hypertension Atherosclerosis Sudden cardiac death

From: Cohen SC et al, New England Journal of Medicine 325: , 1991 Psychological stress increases susceptibility to the common cold

Effects of chronic stress GI system: worsens ulcers Immune system: immunosuppression (increased autoimmune diseases, increased infections) Endocrine system: type II diabetes Growth: retards growth in children, induces weight and bone loss in adults Cardiovascular system: Hypertension Atherosclerosis Sudden cardiac death

From: Mooy J et al, Diabetes Care, 23:1443, 2005 Stress promotes type II diabetes

Effects of chronic stress GI system: worsens ulcers Immune system: immunosuppression (increased autoimmune diseases, increased infections) Endocrine system: type II diabetes Growth: retards growth in children, induces weight and bone loss in adults Cardiovascular system: Hypertension Atherosclerosis Sudden cardiac death

Leor, J. et al. N Engl J Med 1996;334: Daily numbers of Deaths Listed by the Department of Coroner of Los Angeles County from January 10 through 23, 1991, 1992, 1993, and 1994 Emotional stress can trigger cardiac events in at risk individuals: Earthquake occurred early in the morning of Jan 17, 1994 in Los Angeles

Fig involved in processing memories related to stress amygdala

Neuroanatomical correlates of chronic stress in hippocampus Hippocampus has receptors for cortisol Loss of neurons, loss of dendrites and synapses with chronic stress Decreased volume of hippocampus in patients with PTSD, severe depression Same kind of reduction in volume in patients with Cushings disease, a condition of excess cortisol

Block oxytocin receptors in the brain Stress  heart rate  cortisol Stress    heart rate    cortisol Control treatment Conclusion: Oxytocin reduces the cardiovascular responses to stress Wysol, A et al, J Physiol Pharmacol, 59(Suppl 5): , 2008